For the past 20 years this work has been supported by NIH. As a result of these studies ECLS (also known as extracorporeal membrane oxygenation, ECMO), has been studied in the laboratory, evaluated in patients, and has become standard treatment for severe respiratory failure in newborn infants. In the past 3. years, pilot clinical studies in pediatric and adult patients with severe respiratory failure look very encouraging. There are now over 80 ECMO centers worldwide, attaining survival rates of 80-95% in moribund newborn infants and 50-6O% in older children and adults. Our cost effectiveness and morbidity study in neonates demonstrated that ECMO improved survival while decreasing morbidity and hospital costs. Having established that ECMO is not only feasible but standard therapy in term neonates, and with encouraging preliminary results in premature infants and older children, we now propose to improve and simplify the technique based on the following rationale. The problems which limit the final phase of development of ECLS are thrombosis and bleeding, complexity and expense. Elimination of thrombosis, microembolism, and bleeding will extend the safe application of ECLS to one month and will permit application to new groups of patients including premature infants and surgical patients. We have demonstrated instead that ECLS can be carried out without bleeding, clotting or heparin. We now plan to study the physiology of ECLS without heparin. New catheters will simplify routine percutaneous vascular access through a single vein. Total automation will improve safety while decreasing expense. With these improvements in technology, ECLS can be used to facilitate direct treatment of the lung made possible by extracorporeal gas exchange.